The present invention relates to a method of purifying whey separated from lactic acid fermentation liquid by electrodialysis. The whey contains angiotensin-converting enzyme inhibiting peptides. The peptides obtained in the purified whey according to the present invention can be used for anti-high blood pressure agent or foods, when the whey is further treated for oral administration.
The angiotensin-converting enzyme, hereinafter referred to as ACE, is mainly present in lungs and vascular endothelial cells, and acts on angiotensin I (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu SEQ ID No:1) to remove a dipeptide (His-Leu) at its c-terminal and to form angiotensin II, which has a strong blood pressure increasing activity. The ACE also has an ability to decompose and to inactivate bradykinin which decreases blood pressure. Thus, the ACE acts to increase blood pressure by producing angiotensin II on the one hand, while decomposing bradykinin to increase blood pressure. Accordingly, when the angiotensin-converting enzyme is inhibited, high blood pressure could decrease, and many drugs which contain the angiotensin-converting enzyme inhibitor have been developed and used for anti-high blood pressure.
Certain peptides were recently found to be useful, being as low in toxicity and highly safe anti-high blood pressure agents, and natural and synthetic peptides are reported to be possible anti-high blood pressure drugs (Japanese Patent Publication No.120,225/1991). It is also known that peptides containing Ile-Pro-Pro (hereinafter referred to as IPP) or Val-Pro-Pro (hereinafter referred to as VPP) as its basic peptide structure have ACE inhibiting properties, and that these peptides can be produced in large amounts by culturing certain lactic acid bacteria, or lactic acid bacteria and yeast (Japanese patents Nos.2,782,142 and 2,782,153). Drugs or foods consisting of the peptides are proposed to be highly safe and useful in a small amount for decreasing high blood pressure in forms of oral administration, when the cultured liquid is treated for purification and separation.
It may be possible to use the fermentation liquid as obtained in accordance with the processes described in the above patents as the ACE-inhibiting drugs or foods containing the ACE inhibiting peptides (hereinafter referred to as ACEI peptides). However, it may have poor palatability for oral intake, and is not appropriate to drink without further purification processes, because they contain lactic acid and some other substances to some extent. Accordingly, it is desirable to remove substances other than the ACEI peptides from the liquid. Drugs or foods in a dry form including the peptides in more concentrated form than the liquid are more useful. Proteins and the ACEI peptides having IPP or VPP as its basic peptide structure, which are produced by culturing lactic acid bacteria or lactic acid bacteria and yeast are partly hydrolyzed to form IPP and VPP in the cultured broth.